Synthesis, structure and biological activity of CIA and CIB, two α-conotoxins from the predation-evoked venom of Conus catus

Giribaldi, Julien, Wilson, David, Nicke, Annette, El Hamdaoui, Yamina, Laconde, Guillaume, Faucherre, Adèle, Maati, Hamid Moha Ou, Daly, Norelle L., Enjalbal, Christine, and Dutertre, Sébastien (2018) Synthesis, structure and biological activity of CIA and CIB, two α-conotoxins from the predation-evoked venom of Conus catus. Toxins, 10 (6). 222. pp. 1-12.

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Abstract

Cone snails produce a fast-acting and often paralyzing venom that is usually injected into their prey or predator through a hypodermic needle-like modified radula tooth. Many diverse compounds are found in their venom including small molecules, peptides and enzymes. However, peptidic toxins called conotoxins (10-40 residues and 2-4 disulfide bonds) largely dominate these cocktails. These disulfide rich toxins are very valuable pharmacological tools for investigating the function of ions channels, G-protein coupled receptors, transporters and enzymes. Here, we report on the synthesis, structure determination and biological activities of two -conotoxins, CIA and CIB, found in the predatory venom of the piscivorous species Conus catus. CIA is a typical 3/5 -conotoxin that blocks the rat muscle type nAChR with an IC50 of 5.7 nM. Interestingly, CIA also inhibits the neuronal rat nAChR subtype 32 with an IC50 of 2.06 M. CIB is a 4/7 -conotoxin that blocks rat neuronal nAChR subtypes, including 32 (IC50 = 128.9 nM) and 7 (IC50 = 1.51 M). High resolution NMR structures revealed typical -conotoxin folds for both peptides. We also investigated the in vivo effects of these toxins on fish, since both peptides were identified in the predatory venom of C. catus. Consistent with their pharmacology, CIA was highly paralytic to zebrafish (ED50 = 110 g/kg), whereas CIB did not affect the mobility of the fish. In conclusion, CIA likely participates in prey capture through muscle paralysis, while the putative ecological role of CIB remains to be elucidated.

Item ID: 54592
Item Type: Article (Research - C1)
ISSN: 2072-6651
Keywords: conotoxins, Conus catus, electrophysiology, in vivo, nicotinic receptors, structure, synthesis
Copyright Information: © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Funders: French National Research Agency (ANR), Australian Institute of Tropical Health and Medicine (AITHM)
Projects and Grants: ANR-16-CE34-0002, AITHM Capacity Building Grant
Date Deposited: 18 Jul 2018 07:50
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1101 Medical Biochemistry and Metabolomics > 110106 Medical Biochemistry: Proteins and Peptides (incl Medical Proteomics) @ 100%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 100%
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